We have described an outbreak of simian acquired immune deficiency syndrome (SAIDS) in rhesus macaques at the California Primate Research Center (CPRC), readily reproduced the disease, identified and characterized the etiological agent and defined the major natural history features. SAIDS is caused by an exogenous type D retrovirus (SRV-1) related to but distinct from the Mason-Pfizer monkey virus. The virus is pantropic for lymphocytes (i.e., infects both T and B cells) and also grows readily in macrophages and certain epithelial cells. Koch's postulates have been met including induction of fatal SAIDS wtih molecularly cloned SRV-1. Other simian retroviruses including STLV-1 and STLV-III have been ruled out as causes of SAIDS at the CPRC. We have found a second serotype of this Type D virus in association with SAIDS and retroperitoneal fibrosis in Celebes and rhesus macaques at the Oregon Primate Center. The SAIDS viruses appear widespread in primate facilities. SRV-1 has been totally sequenced and a novel genetic structure revealed. It is not closely related to the human AIDS virus nor to the animal lentiviruses. An inactivated SRV-1 vaccine has protected monkeys against challenge with this virulent virus. This proposal is directed at gaining further knowledge of retrovirus induced immunosuppressive disease in monkeys by; 1) defining the temporal and spatial expression of virus and the virus induced immunological defects, 2) identifying the host and viral determinants of the disease. SAIDS is a good model for AIDS because it is a spontaneous retroviral infection that causes a fatal immunosuppressive disease in its natural host. These studies will be carried out by a multidsiciplinary team of investigators at the CPRC and will take advantage of productive collaborations with NIH, Industry, other Universities and other Primate Centers.